Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study
, Isaac Subirana 1,4, Nadia García-Mateo 5, Pilar Cidad 5, Dani Muñoz-Aguayo 6,7, Eulàlia Puigdecanet 3, Lara Nonell 8, Joan Vila 1,4, Felipe M. Crepaldi 1, David de Gonzalo-Calvo 2,9,10, Vicenta Llorente-Cortés 2,9,10, María Teresa Pérez-García 5, Roberto Elosua 2,3,11, Montserrat Fitó 6,7 and Jaume Marrugat 1,2,*
Francesca Pagano
Round 1
Reviewer 1 Report
Dégano et al. aimed to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. They identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, and 1 circulating microRNA that improved CAD risk classification.
Although the findings are of potential interest, there are several major limitations and concerns.
- The manuscript includes numerous data which make the reader confused. Please summarize the data and convert the manuscript to be more reader friendly.
- The author noted that the miRNA improved CAD risk classification, but no ROC curves were provided. (Please have a look at reference [17])
- It is unclear why the author needed two types of cohorts.
- The manuscript seems to be too long.
Author Response
"Please see the attachment."
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors collected in vitro evidence of miRNA expression changes from primary endothelial and smooth muscle cells cultures treated with OxLDL. They established a list of responsive miRNAs and added some known miRNAs associated with CAD to perform a screening in serum samples from healthy and CVD patients (MI,CAD). This study merges previously known and new miRNA with potential association to future development of CAD, and includes miR-143-3p in the predicatore of CAD risk..
The study is overall well conceived and designed, the data are sound and the all the relevant informations were reported. In addition the authors clearly present and discuss the limits of the study.
I have some minor recommendations:
- please state on each table wether you show the adjusted p-value or not.
- I would suggest to add some more content in the target analysis specific for miR-143-3. The authors should consider adding some in vitro evidence in their system of the miRNA action (e.g. checking for known target in the specific system-EC and VSMCs-). This would add a relevant information regarding the protective role of this miRNA in CAD development
Author Response
"Please see the attachment."
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The manuscript can be accepted in the current form.
Author Response
We want to thank the reviewer for revising our manuscript again.
